COPD treatment consists of drug therapies to alleviate the patient’s symptoms, stabilize lung function, and reduce the patient’s risk of COPD exacerbation (increased symptoms that require urgent and additional medical treatments). The mainstay of COPD treatment is a class of drugs called “anti-cholinergics”. These drugs prevent the binding of acetylcholine to the M3 receptors on the airway surface. The brain signals the lung to release acetylcholine in response to the lung’s reaction to toxins, such as from tobacco smoke or environmental pollution, generating a repeating cycle of signaling along the nerve pathways between the lung and the brain. Acetylcholine stimulates airway bronchoconstriction and the production of excess mucus, which causes breathing difficulties and worsened symptoms in patients with COPD. Thus anti-cholinergic drugs can alleviate symptoms and improve breathing by preventing uptake of acetylcholine in the lungs of people with COPD.
Rationale for Targeted Lung Denervation
In some COPD patients, however, the constant cycle of nerve signaling and chronic airway inflammation, reflex bronchoconstriction, and bacterial or viral toxins creates a state of heightened neural sensitivity, called airway hyper-responsiveness. This can be thought of as the pulmonary system on “permanent high alert” which results in an over-exaggerated reaction to stimuli such as air pollution, allergens, or second-hand smoke. This causes flooding of acetylcholine release which stimulates airway bronchoconstriction and the production of excess mucus. These patients may therefore suffer from frequent exacerbations which their COPD medications cannot adequately prevent.
The goal of TLD is to disrupt pulmonary nerve input to the lung to reduce the release of acetylcholine. Targeting of acetylcholine is thus mechanistically similar to the therapeutic strategy of anti-cholinergic drugs, except that TLD achieves its benefit in a single bronchoscopic procedure instead of via inhaled medicines that must be taken daily. Denervation of the lung interrupts nerve signaling to and from the lung, which reduces acetylcholine release, allowing airway smooth muscle to relax, and mucous secretion to decrease. The concept is thus to move the pulmonary system from a state of “high alert” (hyper-reactivity) which is associated with increased exacerbations and symptom burden, to a state of “low alert” (diminished hyper-reactivity) to improve symptom tolerance, decrease symptom burden and thereby decrease COPD exacerbations.
For an overview of TLD’s mechanism of action, please click here.